ArticleOrthopaedic surgery2021
Inhibition of the P53/P21 Pathway Attenuates the Effects of Senescent Nucleus Pulposus Cell-Derived Exosomes on the Senescence of Nucleus Pulposus Cells.
Article in Orthopaedic surgery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations.Advanced healthcare materials · 2022Pooled it
- Removal of aging microenvironment of bone defects can effectively promote bone defect repair.Journal of translational medicine · 2026Article
- Article
- Senolytic treatment for low back pain.Science advances · 2025Article
- Nano-Drug Delivery System Targeting the Oxidative Stress Microenvironment: A Prospective Strategy for Intervertebral Disc Degeneration Treatment.International journal of nanomedicine · 2025Review
- Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.Molecular diagnosis & therapy · 2024Review
- Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway.Scientific reports · 2024Article
- Palmitic acid induces lipid droplet accumulation and senescence in nucleus pulposus cells via ER-stress pathway.Communications biology · 2024Article
- Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc.JOR spine · 2024Article
- Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities.Biomolecules · 2023Review
- [Advances in the role of extracellular vesicles in intervertebral disc degeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2023Article
- Intervertebral disc degeneration-Current therapeutic options and challenges.Frontiers in public health · 2023Review
- Spermidine Retarded the Senescence of Multipotent Mesenchymal Stromal CellsStem cells international · 2023Article
- Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging.International journal of molecular sciences · 2022Article
- Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration.Bioactive materials · 2022Article
- Insights into Exosome in the Intervertebral Disc: Emerging Role for Disc Homeostasis and Normal Function.International journal of medical sciences · 2022Review
- Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe purpose of this paper is to investigate the effects of senescent nucleus pulposus cell (NPC)-derived exosomes (SNPC-Exo) and the roles of the P53/P21 pathway on the senescence of NPC.
methodsThe senescent phenotypes of NPC were induced by interleukin-1β treatment. SNPC-Exo was extracted from the culture medium of senescent NPC and purified by differential centrifugation. The structure of SNPC-Exo was identified by transmission electron microscopy and western blot analysis was used to determine the exosomal marker proteins CD63 and Tsg101. Western blot analysis was performed to determine the relative expression levels of P16, P21, and P53 in NPC. Senescence-associated β-galactosidase (SA-β-gal) staining was used to stain the senescent NPC and a phase contrast microscope was used to observe and count the SA-β-gal staining of NPC. The proliferation of SNPC-Exo-treated NPC was assessed using growth curve analysis and the colony formation assay. The cell cycle of SNPC-Exo-treated NPC was determined by flow cytometry. NPC were transfected with siRNA to knock down P53 and P21 expression.
resultsInterleukin-1β-treated NPC had a higher percentage of SA-β-gal positive cells (45%) than the control group (20%) and showed an increase in the relative expression of P16, P21, and P53 (P < 0.05). SNPC-Exo were positive for exosomal marker protein CD63 and Tsg 101 and negative for calnexin, and successfully internalized as previously described. SNPC-Exo-treated NPC showed an increase in the relative expression of P21 and P53 (P < 0.05). Compared with the control group, the SNPC-Exo-treated NPC showed a lower growth rate (3 times lower on the 5th day and 2 times lower on the 7th day), fewer colony-forming units (12.0%), and a higher percentage of SA-β-gal-positive NPC (50.0%). The SNPC-Exo-treated NPC contained more G1 phase cells (68.0%) and fewer S phase (15.5%) cells than the control group (53.0% in G1 phase, 33.5% in S phase). The expression of P21 and P53 significantly decreased in SNPC-exo-treated NPC after siRNA transfection (P < 0.05), followed by a higher growth rate (2 times higher on the 5th day and 1.5 times higher on the 7th day) and lower percentage of SA-β-gal-positive NPC (22.5%). Moreover, the inhibition of the P53/P21 pathway promoted the SNPC-Exo-treated NPC to enter the S phase (from 15.5% to 25.3%).
conclusionThe inhibition of the P53/P21 pathway attenuated the senescence of NPC induced by SNPC-Exo.
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